Inflammatory ArthritisCCPNCT02012764
The CCP Study: Coordinated Programme to Prevent Arthritis - Can We Identify Arthritis at a Pre-clinical Stage ?
An observational study of Inflammatory Arthritis and Rheumatoid Arthritis, run by University of Leeds at 1 site in United Kingdom.
Trial summary
This is a 12-month, prospective, observational cohort trial involving Primary Care Trusts (PCTs) wishing to take part in the study and the Early Arthritis Clinic (Anti-CCP sub-clinic) at Chapel Allerton Hospital. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Arthritis, Rheumatoid Arthritis
- How many people
- 4,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2007to 30 Jun 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients who are attending GP Practices in the Yorkshire and surrounding regions.
Who may be able to join
- For the purpose of this study, "musculoskeletal complaint" is defined as any new joint / muscular symptoms, including (but not limited to)
- Rotator cuff tendonitis / subacromial bursitis
- Carpal tunnel syndrome
- Tendonitis e.g. epicondylitis "New" complaint is defined as a symptom in which the patient has not previously reported to their GP.
- GP and Musculoskeletal referred patients:
- Subject must fulfil all of the following conditions or characteristics in order to be considered for study enrolment or participation:
Show all 15Show fewer
- Is age > 18 years
- Has a new musculoskeletal complaint or has a family member with RA
- Is capable of understanding and signing an informed consent form
- Rheumatology Clinic referred patients:
- Subject must fulfil all of the following conditions or characteristics in order to be considered for study enrolment or participation:
- Is age > 18 years
- Has a new musculoskeletal complaint
- Is capable of understanding and signing an informed consent form
- Has tested CCP Ab positive
Who cannot join
- GP and Musculoskeletal referred patients:
- Subjects with any of the following conditions or characteristics will be excluded
- Patients with clinical synovitis
- Patient fulfils 1987 ACR Criteria or the 2010 ACR/EULAR criteria for RA
- For the MRI imaging component, the following exclusions will apply; pacemaker, surgical clips within the head, certain inner ear implants, neuro-electrical stimulators or metal fragments within the eye or head or eGFR < 45 ml/min/1.73 m2. In patients with previous penetrating trauma to the eye, or patients at high risk of previous metal foreign body injury to the eye (e.g. welding), skull x-ray will be performed; these patients may be included in the absence of residual metal fragments on x-ray.
- Rheumatology clinic referred patients:
Show all 10Show fewer
- Subjects with any of the following conditions or characteristics will be excluded
- Patient has tested CCP Ab negative
- Patient fulfils 1987ACR Criteria or the 2010 ACR/EULAR criteria for RA
- For the MRI imaging component, the following exclusions will apply; pacemaker, surgical clips within the head, certain inner ear implants, neuro-electrical stimulators or metal fragments within the eye or head or eGFR < 45 ml/min/1.73 m2. In patients with previous penetrating trauma to the eye, or patients at high risk of previous metal foreign body injury to the eye (e.g. welding), skull x-ray will be performed; these patients may be included in the absence of residual metal fragments on x-ray.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Chapel Allerton Hospital : Leeds Institute of Rheumatic and Musculoskeletal Medicine
Leeds, West Yorkshire, LS7 4SA
About this study
This is a 12-month, prospective, observational cohort trial involving Primary Care Trusts (PCTs) wishing to take part in the study and the Early Arthritis Clinic (Anti-CCP sub-clinic) at Chapel Allerton Hospital. The approximate duration of subject participation will be 12 months and the approximate total duration of the study will be 10 years. Patients who have not developed inflammatory arthritis within the 12 month period will have the opportunity to continue follow up within the clinic on an annual basis with additional visits as clinically indicated until the development of IA.
Read the detailed description
There is accumulating evidence for the need to identify patients with rheumatoid arthritis (RA) early. Damage occurs early and early treatment is effective. Clearly there is a need to improve ways of identifying these patients.
It is recognised that patients with RA often have non-specific musculoskeletal complaints in the months or years prior to development of RA (unpublished observations). Family members of patients with RA are also at greater risk of developing RA.
Given we know that earlier identification of patients enables earlier treatment and this leads to better long-term outcomes, we need a method of identifying patients at the pre-clinical stage of disease.
C-reactive protein (CRP) is an acute phase reactant, produced by the liver, primarily in response to stimulation by interleukin-6 (IL-6). The lower limit of detection of routine CRP is 8mg/dL (or higher), yet the mean CRP in the general population is <2mg/dL11 (as measured by high sensitivity assays). Therefore, patients with early RA may have low-grade inflammation not detected by routine CRP. This has been demonstrated in patients with established disease12, but no studies have been done in early disease. Disease activity variables correlated with increases in highly-sensitive CRP (hs-CRP) and hs-CRP was better than ESR at predicting disease activity and severity12. Interestingly, on retrospective analysis of blood donor serum, increased levels of hs-CRP have been noted in RA patients during the pre-clinical phase, most commonly within the two years prior to symptom onset13. This suggests immunologic changes occur prior to the development of the symptomatic stage and provides an exciting tool for assisting in the diagnosis of very early inflammatory disease
- Conditions
- Inflammatory Arthritis, Rheumatoid Arthritis
- Keywords
- Anti-CCP antibody, Inflammatory arthritis, Rheumatoid arthritis, Musculoskeletal symptom
- Medical subject headings
- Arthritis, Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Musculoskeletal symptoms - Pre diagnosis | Patients presenting with non-specific musculoskeletal complaints at risk of development of RA. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-CCP Ab (+).
The primary objective of this study is to determine the proportion of community patients with new-onset, non-specific musculoskeletal complaints who are anti-CCP Ab (+).
Measured: 12 years
Secondary outcomes (5)
Anti-CCP positive developing I.A
Secondary objectives in this study include:
- The number of anti-CCP positive patients who develop an inflammatory arthritis by 12 months / after 12 months.
- Defined as symptoms and signs of synovitis.
- Synovitis is defined as the presence soft tissue swelling and at least 1 of the following 2 criteria; tenderness or decreased range of motion.
Measured: 1 year
Anti-CCP positive developing RA
The number of anti-CCP positive patients who develop RA by 12 months/ after 12 months (defined by 1987 ACR and the 2010 ACR/EULAR criteria).
Measured: 1 year
Presenting complaints
To document the initial presenting complaint of all patients (anti-CCP positive and negative)
Measured: 1 week
Predictors for the development of an IA.
To determine usefulness of hs-CRP in predicting development of an IA in patients with positive anti-CCP Ab.
To determine usefulness of MRI and HRUS in predicting development of an IA in patients with positive anti-CCP Ab.
Measured: 12 years
First degree familymembers who are anti-CCP Ab (+)
To determine the percentage of people with family members who have RA who are anti-CCP Ab (+)
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study startJan 2007
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Inflammatory ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 4,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Principal investigator, Paul Emery, University of Leeds
- Investigators
- Paul Emery, Study chair, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012764
- Sponsor's protocol ID
- RR06/7674
- Other IDs
- 06/Q1205/169
- Acronym
- CCP
- Status last verified
- Mar 2025
- First submitted
- 8 Nov 2013
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Garcia-Montoya L, Kang J, Duquenne L, Di Matteo A, Harnden K, Nam JL, Chowdhury R, Wakefield RJ, Mankia KS, Emery P. Association between joint tenderness, patient-reported joint pain and ultrasound abnormalities in anti-CCP positive individuals at risk of rheumatoid arthritis: a cross-sectional study from a Leeds (UK) cohort. BMJ Open. 2026 Jun 4;16(6):e117366. doi: 10.1136/bmjopen-2026-117366.
PubMed 42242739Siddle HJ, Wilson M, Nam JL, Garcia-Montoya L, Duquenne L, Mankia K, Emery P, Hensor EMA. A multivariable prediction model to identify anti-CCP positive people in those with non-specific musculoskeletal symptoms in primary care. Rheumatology (Oxford). 2025 Jun 1;64(6):3947-3956. doi: 10.1093/rheumatology/keae653.
PubMed 39656784Garcia-Montoya L, Kang J, Duquenne L, Di Matteo A, Nam JL, Harnden K, Chowdhury R, Mankia K, Emery P. Factors associated with resolution of ultrasound subclinical synovitis in anti-CCP-positive individuals with musculoskeletal symptoms: a UK prospective cohort study. Lancet Rheumatol. 2024 Feb;6(2):e72-e80. doi: 10.1016/S2665-9913(23)00305-3.
PubMed 38267105Garcia-Montoya L, Nam JL, Duquenne L, Villota-Eraso C, Di Matteo A, Hartley C, Mankia K, Emery P. Prioritising referrals of individuals at-risk of RA: guidance based on results of a 10-year national primary care observational study. Arthritis Res Ther. 2022 Jan 18;24(1):26. doi: 10.1186/s13075-022-02717-w.
PubMed 35042555Ouboussad L, Hunt L, Hensor EMA, Nam JL, Barnes NA, Emery P, McDermott MF, Buch MH. Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis. Arthritis Res Ther. 2017 Dec 22;19(1):288. doi: 10.1186/s13075-017-1492-9.
PubMed 29273071Nam JL, Hensor EM, Hunt L, Conaghan PG, Wakefield RJ, Emery P. Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis. Ann Rheum Dis. 2016 Dec;75(12):2060-2067. doi: 10.1136/annrheumdis-2015-208235. Epub 2016 Jan 22.
PubMed 26802181Nam JL, Hunt L, Hensor EM, Emery P. Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study. Ann Rheum Dis. 2016 Aug;75(8):1452-6. doi: 10.1136/annrheumdis-2015-207871. Epub 2015 Sep 22.
PubMed 26395501Rakieh C, Nam JL, Hunt L, Hensor EM, Das S, Bissell LA, Villeneuve E, McGonagle D, Hodgson R, Grainger A, Wakefield RJ, Conaghan PG, Emery P. Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study. Ann Rheum Dis. 2015 Sep;74(9):1659-66. doi: 10.1136/annrheumdis-2014-205227. Epub 2014 Apr 12.
PubMed 24728331
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The CCP Study: Coordinated Programme to Prevent Arthritis - Can We Identify Arthritis at a Pre-clinical Stage ?
- ClinicalTrials.gov ID
- NCT02012764
- Acronym / sponsor ID
- CCP / RR06/7674
- Conditions
- Inflammatory Arthritis, Rheumatoid Arthritis
- Keywords
- Anti-CCP antibody, Inflammatory arthritis, Rheumatoid arthritis, Musculoskeletal symptom
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 4,000 participants (estimated)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- Jan 2007
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 12-month, prospective, observational cohort trial involving Primary Care Trusts (PCTs) wishing to take part in the study and the Early Arthritis Clinic (Anti-CCP sub-clinic) at Chapel Allerton Hospital. The approximate duration of subject participation will be 12 months and the approximate total duration of the study will be 10 years. Patients who have not developed inflammatory arthritis within the 12 month period will have the opportunity to continue follow up within the clinic on an annual basis with additional visits as clinically indicated until the development of IA.
Detailed description
There is accumulating evidence for the need to identify patients with rheumatoid arthritis (RA) early. Damage occurs early and early treatment is effective. Clearly there is a need to improve ways of identifying these patients.
It is recognised that patients with RA often have non-specific musculoskeletal complaints in the months or years prior to development of RA (unpublished observations). Family members of patients with RA are also at greater risk of developing RA.
Given we know that earlier identification of patients enables earlier treatment and this leads to better long-term outcomes, we need a method of identifying patients at the pre-clinical stage of disease.
C-reactive protein (CRP) is an acute phase reactant, produced by the liver, primarily in response to stimulation by interleukin-6 (IL-6). The lower limit of detection of routine CRP is 8mg/dL (or higher), yet the mean CRP in the general population is <2mg/dL11 (as measured by high sensitivity assays). Therefore, patients with early RA may have low-grade inflammation not detected by routine CRP. This has been demonstrated in patients with established disease12, but no studies have been done in early disease. Disease activity variables correlated with increases in highly-sensitive CRP (hs-CRP) and hs-CRP was better than ESR at predicting disease activity and severity12. Interestingly, on retrospective analysis of blood donor serum, increased levels of hs-CRP have been noted in RA patients during the pre-clinical phase, most commonly within the two years prior to symptom onset13. This suggests immunologic changes occur prior to the development of the symptomatic stage and provides an exciting tool for assisting in the diagnosis of very early inflammatory disease
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Musculoskeletal symptoms - Pre diagnosis | – | –Patients presenting with non-specific musculoskeletal complaints at risk of development of RA. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who are attending GP Practices in the Yorkshire and surrounding regions.
Key inclusion criteria (15 listed)
- For the purpose of this study, "musculoskeletal complaint" is defined as any new joint / muscular symptoms, including (but not limited to)
- Rotator cuff tendonitis / subacromial bursitis
- Carpal tunnel syndrome
- Tendonitis e.g. epicondylitis "New" complaint is defined as a symptom in which the patient has not previously reported to their GP.
- Subject must fulfil all of the following conditions or characteristics in order to be considered for study enrolment or participation:
Key exclusion criteria (10 listed)
- Subjects with any of the following conditions or characteristics will be excluded
- Patients with clinical synovitis
- Patient fulfils 1987 ACR Criteria or the 2010 ACR/EULAR criteria for RA
- For the MRI imaging component, the following exclusions will apply; pacemaker, surgical clips within the head, certain inner ear implants, neuro-electrical stimulators or metal fragments within the eye or head or eGFR < 45 ml/min/1.73 m2. In patients with previous penetrating trauma to the eye, or patients at high risk of previous metal foreign body injury to the eye (e.g. welding), skull x-ray will be performed; these patients may be included in the absence of residual metal fragments on x-ray.
- Subjects with any of the following conditions or characteristics will be excluded
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Anti-CCP Ab (+).
Time frame: 12 years
The primary objective of this study is to determine the proportion of community patients with new-onset, non-specific musculoskeletal complaints who are anti-CCP Ab (+).
5 secondary outcomes
Anti-CCP positive developing I.A
Time frame: 1 year
Anti-CCP positive developing RA
Time frame: 1 year
Presenting complaints
Time frame: 1 week
Predictors for the development of an IA.
Time frame: 12 years
First degree familymembers who are anti-CCP Ab (+)
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Derived from this study: PubMed 42242739Garcia-Montoya L, Kang J, Duquenne L, Di Matteo A, Harnden K, Nam JL, Chowdhury R, Wakefield RJ, Mankia KS, Emery P. Association between joint tenderness, patient-reported joint pain and ultrasound abnormalities in anti-CCP positive individuals at risk of rheumatoid arthritis: a cross-sectional study from a Leeds (UK) cohort. BMJ Open. 2026 Jun 4;16(6):e117366. doi: 10.1136/bmjopen-2026-117366.
- Derived from this study: PubMed 39656784Siddle HJ, Wilson M, Nam JL, Garcia-Montoya L, Duquenne L, Mankia K, Emery P, Hensor EMA. A multivariable prediction model to identify anti-CCP positive people in those with non-specific musculoskeletal symptoms in primary care. Rheumatology (Oxford). 2025 Jun 1;64(6):3947-3956. doi: 10.1093/rheumatology/keae653.
- Derived from this study: PubMed 38267105Garcia-Montoya L, Kang J, Duquenne L, Di Matteo A, Nam JL, Harnden K, Chowdhury R, Mankia K, Emery P. Factors associated with resolution of ultrasound subclinical synovitis in anti-CCP-positive individuals with musculoskeletal symptoms: a UK prospective cohort study. Lancet Rheumatol. 2024 Feb;6(2):e72-e80. doi: 10.1016/S2665-9913(23)00305-3.
- Derived from this study: PubMed 35042555Garcia-Montoya L, Nam JL, Duquenne L, Villota-Eraso C, Di Matteo A, Hartley C, Mankia K, Emery P. Prioritising referrals of individuals at-risk of RA: guidance based on results of a 10-year national primary care observational study. Arthritis Res Ther. 2022 Jan 18;24(1):26. doi: 10.1186/s13075-022-02717-w.
- Derived from this study: PubMed 29273071Ouboussad L, Hunt L, Hensor EMA, Nam JL, Barnes NA, Emery P, McDermott MF, Buch MH. Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis. Arthritis Res Ther. 2017 Dec 22;19(1):288. doi: 10.1186/s13075-017-1492-9.
- Derived from this study: PubMed 26802181Nam JL, Hensor EM, Hunt L, Conaghan PG, Wakefield RJ, Emery P. Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis. Ann Rheum Dis. 2016 Dec;75(12):2060-2067. doi: 10.1136/annrheumdis-2015-208235. Epub 2016 Jan 22.
- Derived from this study: PubMed 26395501Nam JL, Hunt L, Hensor EM, Emery P. Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study. Ann Rheum Dis. 2016 Aug;75(8):1452-6. doi: 10.1136/annrheumdis-2015-207871. Epub 2015 Sep 22.
- Derived from this study: PubMed 24728331Rakieh C, Nam JL, Hunt L, Hensor EM, Das S, Bissell LA, Villeneuve E, McGonagle D, Hodgson R, Grainger A, Wakefield RJ, Conaghan PG, Emery P. Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms: a prospective observational cohort study. Ann Rheum Dis. 2015 Sep;74(9):1659-66. doi: 10.1136/annrheumdis-2014-205227. Epub 2014 Apr 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Emery study chair
University of Leeds
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Arthritis and Rheumatoid Arthritis, run by University of Leeds at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-CCP Ab (+). (time frame: 12 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02012764, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.